Radiation Countermeasures (USUHS)
Abstract
For the Uniformed Services University of the Health Sciences/Armed Forces Radiobiology Research Institute (USUHS/AFRRI), this program supports developmental, mission directed research to investigate new concepts and approaches that will lead to advancements in biomedical strategies for preventing and treating the health effects of human exposure to ionizing radiation as well as radiation combined with injuries (burns, wounds, hemorrhage, microbiome, gastrointestinal damage, neurobehavioral deficits, bone marrow damage), termed radiation combined injury. Research findings are focused to advance the understanding and to produce the following: (1) To identify new therapeutics candidates that show promising advancement to further development; (2) To developed novel technologies to minimized the use of animal models in the study of radiation countermeasure effects; (3) To investigate the overall radiation effect by countermeasures in the microbiome and anatomical tissue; (4) To find novel biomarkers, late effects and immunosuppression of radiation injury that can quantitate effects on combat performance decrements; (4) To identify novel therapeutic strategies that will support military operations within a nuclear or radiological environment minimizing ground troops short and long term adverse risk. In addition to the primary achievement of research objectives, the program educates Federal employees as a benefit to the public they serve through Federal service, through support to civil authorities, and in non-Federal professional and academic collaborations. Description: For the Uniformed Services University of the Health Sciences/Armed Forces Radiobiology Research Institute (USUHS/AFRRI), this program supports developmental, mission directed research to investigate new concepts and approaches that will lead to advancements in biomedical strategies for preventing and treating the health effects of human exposure to ionizing radiation as well as radiation combined with injuries (burns, wounds, hemorrhage, microbiome, gastrointestinal damage, neurobehavioral deficits, bone marrow damage), termed radiation combined injury. Research findings are focused to advance the understanding and to produce the following: (1) To identify new therapeutics candidates that show promising advancement to further development; (2) To developed novel technologies to minimized the use of animal models in the study of radiation countermeasure effects; (3) To investigate the overall radiation effect by countermeasures in the microbiome and anatomical tissue; (4) To find novel biomarkers, late effects and immunosuppression of radiation injury that can quantitate effects on combat performance decrements; (4) To identify novel therapeutic strategies that will support military operations within a nuclear or radiological environment minimizing ground troops short and long term adverse risk. In addition to the primary achievement of research objectives, the program educates Federal employees as a benefit to the public they serve through Federal service, through support to civil authorities, and in non-Federal professional and academic collaborations. FY21 Accomplishments: (1)Completed methylome and proteome studies with hematopoietic progenitor cells using murine model. (2)Characterized and correlated the dose and dose rate effect of sub-lethal neutron radiation on genetic and epigenomic perturbations in hematopoietic progenitor cells in male mice. (3)Determined transcriptomic signatures that are correlated with radiation injury, using whole blood transcriptome analysis. (4)Established the gut organ-on-chip model. (5)Identified and tested small molecule countermeasure following Lipinski’s rules. (6)Selected countermeasure therapeutic to test using the gut-organ-on-chip model for radioprotective and radiomitigative potential. (7) Tested long term effect in bone morrow irradiated with 2.5% mice. (8)Characterized injury to lungs, heart, and brain by analyzing biomarkers specific to this organs and vascular endothelial tissue at different radiation doses. (9)Monitored up to six months mice exposed to BPI to study delayed effects of radiation exposure. (10)Screened potential prophylactic countermeasures in PBI with 2.5% model. (11)Established growth conditions for BM endothelium and vascular endothelium in 3D cell culture environment. (12)Established optimal conditions for endothelial/immune cell contact and non/contact co-culture in 3D cell culture environment. (13)Performed gamma radiations with single cultures in 3D cell culture system. (14)Conducted cellular experiments (DNA damage, survival, functions) (15)Performed gamma radiations with endothelium/immune cell 3D cultures. (16)Tested bone morrow and ileu of male and female mice to access levels of cytokine, AKT, MAPK and caspase-3 for organ injury. (17)Tested tissue lysates of bone marrow, ileum and spleen of male and female mice for cytokine and complement component 3. (18)Completed IL-18 studies indicating that IL-18 binding protein (IL-18BP) can be tested as potential drug target. Mice treatment with IL-18BP indicates inhibition of downstream signaling, protecting the mice tissue from radiation by decreasing apoptosis after total body radiation. (19)In 2019/2021, 44 manuscripts were published.
Document Details
- Document Type
- Accomplishment
- Publication Date
- Oct 01, 2023
- Source ID
- 78da182633220c5fbd301c0dc5db95f3